Ionophore-induced secretion of histamine from rat basophil leukemic (RBL-2H3) cells correlated with the hydrolysis of inositol phospholipids but not with the increase in cytosol Ca(2+) ((Ca(2+))) although increased (Ca(2+))) was obligatory for secretion (J. Boil Chem. 262:414 1987). The same pattern was observed for release for arachidonic acid. Moreover, the release of both histamine and arachidonic acid was enhance by activators of protein kinase C and in this circumstance the release was correlated with the increase in (Ca(2+))). The extent of release of histamine and arachidonic acid to ionophore alone, therefore, may be limited by the extent of activation of protein kinase C rather than by the extent of increase in (Ca(2+))). The subsequent mechanisms of release may well differ: the release of arachidonic acid was 4 to 5 times greater with optimal concentrations of A23187 than with optimal concentrations of antigen in the absence or presence of activators of protein kinase C. This was not true for release of histamine for which both ionophore and an activator of protein kinase C were required to match the release induced by optimal concentrations of antigen alone.